Intestinal Microbiota - An Unmissable Bridge to Severe Acute Pancreatitis-Associated Acute Lung Injury

Abstract

Severe acute pancreatitis (SAP), one of the most serious abdominal emergencies in general surgery, is characterized by acute and rapid onset as well as high mortality, which often leads to multiple organ failure (MOF). Acute lung injury (ALI), the earliest accompanied organ dysfunction, is the most common cause of death in patients following the SAP onset. The exact pathogenesis of ALI during SAP, however, remains unclear. In recent years, advances in the microbiota-gut-lung axis have led to a better understanding of SAP-associated lung injury (PALI). In addition, the bidirectional communications between intestinal microbes and the lung are becoming more apparent. This paper aims to review the mechanisms of an imbalanced intestinal microbiota contributing to the development of PALI, which is mediated by the disruption of physical, chemical, and immune barriers in the intestine, promotes bacterial translocation, and results in the activation of abnormal immune responses in severe pancreatitis. The pathogen-associated molecular patterns (PAMPs) mediated immunol mechanisms in the occurrence of PALI via binding with pattern recognition receptors (PRRs) through the microbiota-gut-lung axis are focused in this study. Moreover, the potential therapeutic strategies for alleviating PALI by regulating the composition or the function of the intestinal microbiota are discussed in this review. The aim of this study is to provide new ideas and therapeutic tools for PALI patients.

Inhibition of Pck1 in intestinal epithelial cells alleviates acute pancreatitis via modulating intestinal homeostasis

“…Intestinal homeostasis is disturbed during AP progression which could lead to bacteria translocation, systemic inflammatory response syndrome (SIRS), and multiple organ dysfunction syndromes (MODS) 1,4,41 . Therefore, many studies devoted to explore the mechanism underlying the intestinal barrier dysfunction during AP.…”

Altered gut microbiota in the early stage of acute pancreatitis were related to the occurrence of acute respiratory distress syndrome

“…Gut microbiota activate immune cells, which can migrate from the gut to the lung and assist in resisting systemic inflammatory disease ( He et al., 2017 ; Mjösberg and Rao, 2018 ), and release metabolites and endotoxins to influence host immune response ( Segain et al., 2000 ; Artis, 2008 ; Lin and Zhang, 2017 ). Additionally, gut microbiota dysbiosis damages the integrity of the intestinal barrier and enables bacterial translocation ( Wang et al., 2022 ). Bacteria in the gut can translocate to the lung through the lymphatic or blood circulation systems and thus mediate lung inflammation ( Mukherjee and Hanidziar, 2018 ).…”

“…Dysbiosis of anaerobic bacteria is correlated with intestinal epithelial integrity and promotes overgrowth of pathogenic bacteria ( Hong et al., 2018 ; Zhou and Liao, 2021 ). The proliferation of pathogenic bacteria can consume fatty acids, change intestinal pH, inhibit the growth of probiotics, and damage the gut chemical barrier ( Wang et al., 2022 ). In addition, the overgrowth of pathogens restricts the function of immune cells, such as Tregs, Th2, and B cells; promotes the production of inflammatory factors, such as IL-1β, IL-6, and TNF-α; and thus damages the gut immune barrier ( Zhou and Liao, 2021 ; Wang et al., 2022 ).…”

“…The proliferation of pathogenic bacteria can consume fatty acids, change intestinal pH, inhibit the growth of probiotics, and damage the gut chemical barrier ( Wang et al., 2022 ). In addition, the overgrowth of pathogens restricts the function of immune cells, such as Tregs, Th2, and B cells; promotes the production of inflammatory factors, such as IL-1β, IL-6, and TNF-α; and thus damages the gut immune barrier ( Zhou and Liao, 2021 ; Wang et al., 2022 ). As a normal pathogen, Escherichis-Shigella is associated with epithelial cell injury and is strongly correlated with AP and ARDS severity ( Zhu et al., 2019 ; Pan et al., 2021 ).…”

Intestinal microbiota analysis and network pharmacology reveal the mechanism by which Lianhua Qingwen capsule improves the immune function of mice infected with influenza A virus

“…Both belong to the mucosal immune system, although the intestine and respiratory tract are two separate organs. The latest research has indicated that changes in intestinal microbial composition and function are correlated with the development of lung diseases ("intestine-lung axis") (Bulanda and Wypych, 2022;Chen et al, 2022;Melo-Gonzalez et al, 2022;Shi et al, 2022;Wang L. et al, 2022;Wang Z. et al, 2022). Moreover, available data indicate that intestinal microbes are strongly correlated with clinical symptoms and inflammatory indices of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (Wang H. et al, 2021;Gutierrez-Castrellon et al, 2022;Sencio et al, 2022;Xavier-Santos et al, 2022).…”